Basic NeuroscienceA novel method to study cerebrospinal fluid dynamics in rats

- CSF formation is critical for normal brain health.
- Abnormalities are implicated in brain maldevelopment, degeneration, hydrocephalus.
- In rats, CSF formation has only been measured indirectly.
- We describe a novel method for direct measurement of CSF formation in rats.
- Our method will advance studies on development, aging and hydrocephalus.

BackgroundCerebrospinal fluid (CSF) flow dynamics play critical roles in both the immature and adult brain, with implications for neurodevelopment and disease processes such as hydrocephalus and neurodegeneration. Remarkably, the only reported method to date for measuring CSF formation in laboratory rats is the indirect tracer dilution method (a.k.a., ventriculocisternal perfusion), which has limitations.New methodAnesthetized rats were mounted in a stereotaxic apparatus, both lateral ventricles were cannulated, and the Sylvian aqueduct was occluded. Fluid exited one ventricle at a rate equal to the rate of CSF formation plus the rate of infusion (if any) into the contralateral ventricle. Pharmacological agents infused at a constant known rate into the contralateral ventricle were tested for their effect on CSF formation in real-time.ResultsThe measured rate of CSF formation was increased by blockade of the Sylvian aqueduct but was not changed by increasing the outflow pressure (0-3 cm of H2O). In male Wistar rats, CSF formation was age-dependent: 0.39 ± 0.06, 0.74 ± 0.05, 1.02 ± 0.04 and 1.40 ± 0.06 μL/min at 8, 9, 10 and 12 weeks, respectively. CSF formation was reduced 57% by intraventricular infusion of the carbonic anhydrase inhibitor, acetazolamide.Comparison with existing methodsTracer dilution methods do not permit ongoing real-time determination of the rate of CSF formation, are not readily amenable to pharmacological manipulations, and require critical assumptions. Direct measurement of CSF formation overcomes these limitations.ConclusionsDirect measurement of CSF formation in rats is feasible. Our method should prove useful for studying CSF dynamics in normal physiology and disease models.